crossing96/oncoscreening huggingface dataset:
Ten-Year Oncologic Outcomes Following Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.	PURPOSE: Radical cystectomy is the gold standard for nonmetastatic muscle invasive bladder cancer and for refractory nonmuscle invasive disease. Compared to open radical cystectomy, robot-assisted radical cystectomy has been shown to provide comparable early oncologic outcomes and improved perioperative outcomes. However, there is a paucity of data on long-term oncologic outcomes and concerns about a higher incidence of local recurrence after robot-assisted radical cystectomy. We report 10-year oncologic outcomes following robot-assisted radical cystectomy using a multinational database. MATERIALS AND METHODS: We retrospectively reviewed the prospective International Robotic Cystectomy Consortium database. Consecutive patients who underwent robot-assisted radical cystectomy 10 years ago or earlier were included in analysis. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Kaplan-Meier curves were used to depict recurrence-free, disease specific and overall survival. Multivariate stepwise Cox regression models were applied to identify variables associated with recurrence-free, disease specific and overall survival. RESULTS: We identified 446 patients with a median age of 67 years (IQR 59-76). Of the patients 10% received neoadjuvant chemotherapy, 51% experienced any complication, 23% had high grade complications and 4% died within 3 months of robot-assisted radical cystectomy. Disease was pT3 or greater in 43% of patients and pN+ in 24% while a positive soft tissue surgical margin was observed in 7%. At a median followup of 5 years (IQR 2-10, maximum 14) local and distant recurrence had developed in 15% and 29% of patients, respectively. Ten-year recurrence-free, disease specific and overall survival rates were 59%, 65% and 35%, respectively. Patients with pT3 or greater and pN+ disease showed worse recurrence-free, disease specific and overall survival. CONCLUSIONS: Long-term oncologic outcomes, and recurrence rates and patterns after robot-assisted radical cystectomy seem comparable to those in open series. Advanced disease stage and positive surgical margins remain the main determinants of survival after radical cystectomy.	bladder
ALDH1A1 in patient-derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression.	Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long-term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor-initiating potential, or cancer stem-like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CSC characterization will be the first step towards understanding the mechanisms underlying advanced disease. Here we generated long-term patient-derived cancer cells (PDCs) from bladder cancer patient specimens in spheroid culture, which is favorable for CSC enrichment. Pathological features of bladder cancer PDCs and PDC-dependent patient-derived xenografts (PDXs) were basically similar to those of their corresponding patients' specimens. Notably, CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in PDCs. ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all-trans RA could rescue ALDH1A1 shRNA-suppressed spheroid formation. ALDH inhibitor also reduced the in vivo growth of PDC-derived xenografts. ALDH1A1 knockdown study showed that tubulin beta III (TUBB3) was one of the downregulated genes in PDCs. We identified functional RA response elements in TUBB3 promoter, whose transcriptional activities were substantially activated by RA. Clinical survival database reveals that TUBB3 expression may associate with poor prognosis in bladder cancer patients. Moreover, TUBB3 knockdown was sufficient to suppress PDC proliferation and spheroid formation. Taken together, our results indicate that ALDH1A1 and its putative downstream target TUBB3 are overexpressed in bladder cancer, and those molecules could be applied to alternative diagnostic and therapeutic options for advanced disease.	bladder
Increased miR-323a induces bladder cancer cell apoptosis by suppressing c-Met.	The current study aimed to evaluate the expression and role of miR-323a in the progression of bladder cancer (BC), thereby providing a theoretical basis and potential therapy methods for BC patients. Our data showed that miR-323a levels were significantly reduced in BC tissues compared with those of non-cancerous tissues. Meanwhile, miR-323a was significantly decreased in human BC cell lines (T24, J82, TCCSUP, RT-112) than that in human normal bladder epithelial cell line SV-HUC-1. Furthermore, inhibition of miR-323a markedly enhanced the migration and invasive capacity of T24 and TCCSUP cells. Moreover, overexpression of miR-323a significantly prompted the apoptosis of BC cells. Dual luciferase reporter assay and western blot analysis confirmed that c-Met was a target gene of miR-323a. More importantly, upregulation of c-Met significantly prompted BC cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c-Met was silenced in BC cells. In summary, reduced miR-323a expression in BC contributed to enhanced BC cell proliferation and migration mainly by targeting c-Met.	bladder
(‑)‑Epigallocatechin‑3‑gallate inhibits bladder cancer stem cells via suppression of sonic hedgehog pathway.	Cancer stem cells (CSCs) are associated with the occurrence and metastasis of human malignant tumors, and targeting CSCs is an important strategy for cancer prevention and overcoming drug resistance. (‑)‑Epigallocatechin‑3‑gallate (EGCG), a bioactive polyphenol from green tea, has been studied extensively for its beneficial effects on various tumors including bladder cancer. However, the mechanism underlying the effect of EGCG on bladder CSCs remains poorly understood. Here, the authors investigated the expression of bladder CSCs markers including cluster of differentiation (CD)44, CD133, Oct4, ALDH1A1 and Nanog, and their role in the effect of EGCG on bladder CSCs. EGCG inhibited bladder cancer tumorspheres, downregulated stem cell markers, suppressed the expression of proliferation‑associated proteins in and promoted the apoptosis of bladder CSCs. The effect of EGCG was mediated by the sonic hedgehog signaling pathway, and upregulation of sonic hedgehog signaling pathway components attenuated the suppressive effects of EGCG. Taken together, the results indicated that EGCG could be an important natural compound against bladder CSCs and provide new insights into the effective molecular targeting of bladder CSCs.	bladder
Secular trends in incidence and mortality of bladder cancer in China, 1990-2017: A joinpoint and age-period-cohort analysis.	BACKGROUND: Bladder cancer is closely related to occupational carcinogens, and China is undergoing a rapid industrialization. However, trend of bladder cancer incidence and mortality remains unknown in China. METHODS: Incidence and mortality rates of bladder cancer (1990-2017) were collected for each 5-year age group stratified by gender (males/females) from the Global Burden of Disease (GBD) 2017 study. The average annual percentage change (AAPC) of rates were analyzed by joinpoint regression analysis; age, period and cohort effects on incidence and mortality were simultaneously estimated by age-period-cohort model. RESULTS: Through 1990-2017, age-standardized incidence rates significantly rose in men (AAPC = 0.72%, 95% CI: 0.5%, 0.9%) while decreased in women (-1.25%: -1.6%, -0.9%); age-standardized mortality rates decreased in both men (-1.09%: -1.2%, -0.9%) and women (-2.48%: -2.8%, -2.2%). The joinpoint regression analysis showed the mortality almost decreased in all age groups; while the incidence increased in men for older age groups (from 45 to 49 to 80-84). Moreover, age effect showed the incidence and mortality increased with age; the incidence and mortality increased with time period, while in women period effect stop decreasing and began to increase since 2007; cohort effect showed them decreased with birth cohorts. CONCLUSIONS: The incidence of bladder cancer is increasing in men but mortality decreases in both sexes. Both the incidence and mortality in men substantially increase with age and period, while the rates in women increased with period since 2007. The period effect may indicate the increased risks to bladder cancer in Chinese men. Etiological studies are needed to identify the factors driving these trends of bladder cancer.	bladder
Prognostic value and association with epithelial-mesenchymal transition and molecular subtypes of the proteoglycan biglycan in advanced bladder cancer.	OBJECTIVE: Dysregulation of the extracellular matrix molecule biglycan (BGN) predicts poor survival in several cancer entities. Our study investigated the prognostic impact of BGN in bladder cancer (BC) in 2 independent cohorts and assessed its role in epithelial-mesenchymal transition (EMT) and association with molecular BC subtypes. METHODS: BGN protein expression was correlated with the oncological outcome of 162 patients with BC undergoing radical cystectomy (RC) in a single center and furthermore on gene expression level in the TCGA database. Cut-off values for BGN protein and RNA expression were tested with receiver operating characteristic (ROC) curves. BGN gene expression was correlated with established EMT and BC gene signatures in the TCGA database using gene set enrichment analysis (GSEA). Key EMT and basal/luminal molecular BC subtype markers were correlated with BGN expression and data were shown in a heat map. RESULTS: BGN upregulation in BC cells on the protein level predicted poor oncological survival in the institutional cohort for both univariate (P = 0.007) and multivariate (P = 0.040) analyses. BGN expression was not associated with other clinicopathological parameters. The prognostic value of BGN was validated on the mRNA level in the BC TCGA database (P = 0.002). Both EMT and BC core gene signatures (P < 0.001) correlated with BGN expression in GSEA. BGN gene expression was associated with key indicators of EMT. BGN was associated positively with the molecular basal BC subtype and negatively with the BC luminal subtype. CONCLUSION: BGN is an independent prognosticator for poor survival in BC patients. BGN is associated with the basal molecular BC subtype. EMT might be a key player for BGN driven oncogenesis, as BGN expression correlates with EMT gene signatures.	bladder
Nanophotosensitizer-engineered Salmonella bacteria with hypoxia targeting and photothermal-assisted mutual bioaccumulation for solid tumor therapy.	Bacteria-driven drug-delivery systems have attracted great attention for their enhanced therapeutic specificity and efficacy in cancer treatment. YB1, a particularly attractive genetically modified safe Salmonella Typhimurium strain, is known to penetrate hypoxic tumor cores with its self-driven properties while remarkably avoiding damage to normal tissues. Herein, nanophotosensitizers (indocyanine green (ICG)-loaded nanoparticles, INPs) were covalently attached to the surface of YB1 with amide bonds to develop a biotic/abiotic cross-linked system (YB1-INPs) for tumor precision therapy. YB1 microswimmer retained its viability after efficiently linking with INPs. This YB1-INPs treatment strategy demonstrated specific hypoxia targeting to solid tumors, perfect photothermal conversion, and efficient fluorescence (FL) imaging properties. Benefited from the combined contribution of tumor tissue destruction and the bacteria-attracting nutrients generation after photothermal treatment, the bioaccumulation of YB1-INPs was significantly improved 14-fold compared to no photothermal intervention. Furthermore, YB1-INPs pervaded throughout the large solid tumor (≥500 mm(3)). Under near-infrared (NIR) laser irradiation, YB1-INPs exhibited a dependable and highly efficient photothermal killing ability for eradicating the large solid tumor without relapse. This strategy of bacteria-driven hypoxia-targeting delivery has a great value for large solid tumors therapy with low toxicity and high efficiency.	bladder
The roles and mechanism of IFIT5 in bladder cancer epithelial-mesenchymal transition and progression.	The prognosis of bladder cancer (BCa) depends on several key factors including anatomical site, tumor grade, and stage. In general, muscle-invasive bladder cancer (MIBC) is associated with higher incidence of distant metastasis compared with Non-muscle-invasive bladder cancer (NMIBC). Treatment outcome of the patients with metastatic BCa has been very poor with ~15% of overall survival rate. Thus, it is apparently important to understand the underlying biology for metastatic progression of BCa. Although epithelial-mesenchymal transition (EMT) has long been implicated in BCa metastasis and treatment resistance, the underlying mechanism is not fully understood. In this study, we have identified that the expression of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is positively correlated with pathological characteristics, and predicts a poor prognosis of BCa patients. Since the function of IFIT5 in BCa has not yet been characterized, we demonstrate that IFIT5 can induce EMT, promote cell migration and invasion, and increase the expression of ICAM1 in BCa via down-regulation of mature miR-99a. Moreover, ICAM1 is shown as a direct target of miR-99a. Overall, we conclude that IFIT5 is a new oncogene in BCa.	bladder
SEC11A Expression Is Associated with Basal-Like Bladder Cancer and Predicts Patient Survival.	OBJECTIVES: Bladder cancer (BC) is a common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and induces transforming growth factor-α secretion. In the present study, we analyzed the expression and function of SPC18 protein in human BC. METHODS: Expression of SPC18 was analyzed by immunohistochemistry. RNA interference was used to inhibit SEC11A expression in BC cell lines. For constitutive expression of the SEC11A gene, a SEC11A expression vector was transfected into BC cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Modified Boyden chamber assays were used to examine cell invasiveness. RESULTS: SPC18 was upregulated in 54% of 81 BC cases. SPC18 expression served as an independent prognostic classifier of patients with BC. SPC18-positive BC cases frequently expressed cytokeratin 5/6, a marker of basal-like BC. Cell growth and invasiveness were inhibited by SEC11A knockdown and enhanced by forced expression of SEC11A. CONCLUSION: These results indicate that SPC18 plays an important role in the progression of BC. Specific inhibitors of SPC18 may be promising anticancer drugs for patients with basal-like BC.	bladder
lncRNA TUC338 is a potential diagnostic biomarker for bladder cancer.	Although long noncoding RNA TUC338 has been characterized as an oncogene, its role in bladder cancer is unknown. The purpose of the present study is to investigate the function of TUC338 in bladder cancer. We found that TUC338 was upregulated in early-stage bladder cancer patients and showed early diagnostic values. After surgical resection, plasma levels of TUC338 were significantly downregulated. Moreover, microRNA 10b (miR-10b) was also upregulated in bladder cancer patients. TUC338 and miR-10b were positive and significantly correlated in bladder cancer patients, but not in healthy controls. Bladder cancer cells with TUC338 overexpression showed upregulated miR-10b, while miR-10b overexpression failed to significantly affect TUC338. TUC338 and miR-10b overexpression significantly promoted bladder cancer cell invasion and migration. Therefore, TUC338 may promote bladder cancer at least partially by upregulating miR-10b.	bladder
Does the Use of a Robot Decrease the Complication Rate Adherent to Radical Cystectomy? A Systematic Review and Meta-Analysis of Studies Comparing Open with Robotic Counterparts.	"Introduction: Radical cystectomy (RC) is the mainstay of treatment for muscle-invasive bladder cancer. In 2003, the first robot-assisted radical cystectomy (RARC) was performed and since then many studies, mainly observational, were conducted to compare robotic and open methods. This study aims to assess perioperative outcomes between the two methods based on pooled data from existing literature. Methods: A literature search of articles in English and French languages was performed in three databases (Medline, Embase, and Cochrane) until 30th of June 2018, as well as in urology conference programs and reference lists of included studies. The study protocol was registered at PROSPERO (CRD42018103063). Terms such as ""robotic,"" ""open,"" and ""radical cystectomy"" and synonyms were used for the searching algorithm. The primary outcome was the number of minor and major postoperative complications (Clavien grading system). Risk of bias was assessed with the Cochrane tool and Newcastle-Ottawa scale. Comparison of continuous outcomes was performed with weighted mean differences, while for dichotomous outcomes, odds ratios (ORs) were used. Review Manager 5.3 was used. Results: Fifty-four studies (5 randomized trials and 49 observational) were eligible, including 29,697 patients (6500 in the RARC group and 23,197 in the open radical cystectomy group). Minor complications (grade 1-2) in pooled data of 29 studies were fewer in the RARC group (OR = 0.54, 95% confidence interval [CI]: 0.38-0.76, p < 0.001), a difference persisting after sensitivity analysis for 30 and 90 days. Major complications (grade 3-5) in 31 studies were fewer in the RARC group (OR = 0.78, 95% CI: 0.65-0.94, p = 0.009), but this difference disappeared in the 30-day subanalysis. RARC was associated with lower blood transfusion rates (p < 0.001), lower length of stay (p < 0.001), faster return to regular diet (p < 0.001), and lower postoperative mortality rates (p < 0.001), but longer operating time. Conclusions: RARC appears to be associated with fewer complications and favoring perioperative outcomes in comparison with the open method. Due to the observational nature of most studies, larger randomized trials are needed to confirm these findings."	bladder
Neoadjuvant Chemotherapy Does Not Increase the Morbidity of Radical Cystectomy: A 10-year Retrospective Nationwide Study.	BACKGROUND: Neoadjuvant chemotherapy (NAC) is underutilized in the treatment of bladder cancer (BC). OBJECTIVE: To investigate the effect of NAC on the risk of surgical complications for radical cystectomy (RC) in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS: All radical cystectomies performed in Finland during 2005-2014 were included in the study. Data were collected retrospectively using a web-based data collection platform. Complications were recorded for 90 d using the Clavien classification. Patients treated with NAC were compared to patients receiving RC alone using three cohorts and approaches: the entire cohort, a neoadjuvant period cohort, and a matched cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For all three cohorts, odds ratios (ORs) were estimated using simple binary logistic regression. In addition, a multivariable stratified logistic model with propensity score was used. For the matched cohort analysis, both univariate and adjusted analyses were carried out. RESULTS AND LIMITATIONS: During 2005-2014, 1427 RCs were performed in Finland, of which 1385 were included in the analyses. NAC was introduced in 2008, and 231 patients (16%) were assigned to NAC and 214 (15%) received two or more cycles of chemotherapy. Within 90 d, 61% of patients experienced complications and mortality was 4% (1.9% in the NAC group, and 4.4% in the RC-alone group). In simple binary logistic regression, NAC patients had significantly fewer complications, but this was not observed in multivariable or propensity score analyses. In the matched cohort analyses, no differences in complication rates could be observed. None of the analyses demonstrated higher complication rates in the NAC group. CONCLUSIONS: Our retrospective study reports on nationwide use of NAC for BC and demonstrates that NAC does not increase RC morbidity. PATIENT SUMMARY: Chemotherapy given before radical surgery does not increase severe postoperative complications in the treatment of bladder cancer.	bladder
Familial Urinary Bladder Cancer with Other Cancers.	BACKGROUND: Family risks for urinary tract cancers (excluding kidney cancers) are known, but less is known about whether rare urinary tract cancer subtypes are also familial and if urinary tract cancers share familial risk for other (discordant) cancers. OBJECTIVE: To investigate the impact of family history on urinary tract cancers (International Classification of Diseases version 7 code 181) and discordant cancers. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Family-Cancer Database, the largest family data set in the world, was used to assess familial risks between 86 058 patients with urinary tract cancers and patients with other cancers between 1958 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A Poisson regression model was used to generate relative risks (RRs). RESULTS AND LIMITATIONS: Some 7.0% of patients with urinary tract cancers had a parent or sibling diagnosed with the same cancer, yielding an RR of 1.81 (95% confidence interval [CI] 1.68-1.94). As novel familial findings, we also found that ureter (RR 1.62, 95% CI 1.04-2.53) and transitional cell in situ tumors (RR 2.04, 95% CI 1.49-2.80) were associated with urinary tract cancers. The most consistent discordant familial associations of urinary tract cancers were with smoking-related sites of cancer: lung, stomach, and kidney. Internally consistent familial associations not related to smoking were found for endometrial and thyroid cancers. Familial associations with urinary tract cancers were also found for rare anal, female genital, and cervical cancers. The main limitation was a lack of data on smoking. CONCLUSIONS: Smoking-related cancers were associated with urinary tract cancer. We speculate that familial clustering of endometrial and thyroid cancers with urinary tract cancers may be ascribed to obesity. PATIENT SUMMARY: Diagnosis of bladder cancer in a close family member may be a sign of higher risk among other family members. Patients and family members should be told that bladder cancer is smoking-related and they should be counseled to recognize blood in urine as a possible early sign.	bladder